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Induction of aquaporin 4-reactive antibodies in Lewis rats immunized with aquaporin 4 mimotopes

Tsymala, Irina (author)
Med Univ Vienna, Austria
Nigritinou, Magdalini (author)
Med Univ Vienna, Austria
Zeka, Bleranda (author)
Med Univ Vienna, Austria
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Schulz, Rouven (author)
Med Univ Vienna, Austria
Niederschick, Felix (author)
Med Univ Vienna, Austria
Matkovic, Mia (author)
Med Univ Vienna, Austria
Bauer, Isabel J. (author)
Med Univ Vienna, Austria
Szalay, Michael (author)
Med Univ Vienna, Austria
Schanda, Kathrin (author)
Med Univ Innsbruck, Austria
Lerch, Magdalena (author)
Med Univ Innsbruck, Austria
Misu, Tatsuro (author)
Tohoku Univ, Japan; Tohoku Univ, Japan
Fujihara, Kazuo (author)
Tohoku Univ, Japan; Tohoku Univ, Japan
Bennett, Jeffrey L. (author)
Univ Colorado, CO 80045 USA
Dahle, Charlotte, 1956- (author)
Linköpings universitet,Avdelningen för inflammation och infektion,Medicinska fakulteten,Region Östergötland, Klinisk immunologi och transfusionsmedicin
Pache, Florence (author)
Charite Univ Med Berlin, Germany
Rommer, Paulus (author)
Med Univ Vienna, Austria
Leutmezer, Fritz (author)
Med Univ Vienna, Austria
Illes, Zsolt (author)
Odense Univ Hosp, Denmark; Univ Southern Denmark, Denmark
Leite, Maria Isabel (author)
John Radcliffe Hosp, England
Palace, Jacqueline (author)
John Radcliffe Hosp, England
Scholze, Petra (author)
Med Univ Vienna, Austria
Reindl, Markus (author)
Med Univ Innsbruck, Austria
Lassmann, Hans (author)
Med Univ Vienna, Austria
Bradl, Monika (author)
Med Univ Vienna, Austria
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 (creator_code:org_t)
2020-04-15
2020
English.
In: Acta neuropathologica communications. - : BMC. - 2051-5960. ; 8:1
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Most cases of neuromyelitis optica spectrum disorders (NMOSD) harbor pathogenic autoantibodies against the water channel aquaporin 4 (AQP4). Binding of these antibodies to AQP4 on astrocytes initiates damage to these cells, which culminates in the formation of large tissue destructive lesions in the central nervous system (CNS). Consequently, untreated patients may become permanently blind or paralyzed. Studies on the induction and breakage of tolerance to AQP4 could be of great benefit for NMOSD patients. So far, however, all attempts to create suitable animal models by active sensitization have failed. We addressed this challenge and identified peptides, which mimic the conformational AQP4 epitopes recognized by pathogenic antibodies of NMOSD patients. Here we show that these mimotopes can induce the production of AQP4-reactive antibodies in Lewis rats. Hence, our results provide a conceptual framework for the formation of such antibodies in NMOSD patients, and aid to improve immunization strategies for the creation of animal models suitable for tolerance studies in this devastating disease.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Keyword

Neuromyelitis optica spectrum disorders; Antibodies; Mimotopes; Aquaporin 4; Infections; Animal model

Publication and Content Type

ref (subject category)
art (subject category)

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